China is intent on rolling out its experimental coronavirus vaccines in the hope of securing a ‘first mover’ advantage and using vaccines as a diplomatic tool to cement relationships with grateful countries.
But academics have expressed concerns on transparency and other issues including rushed clinical trials, patients potentially put at risk, and regulatory short cuts being taken in the name of speed.
Streamlining processes to speed up development of much-needed vaccines for COVID-19 with more than 36.2 million cases and over 1 million deaths worldwide – is not unusual. The United States and European countries are funding the scale-up of manufacturing of candidate vaccines in parallel with ongoing clinical trials and policy decisions are being fast-tracked.
Conditions for emergency regulatory approval, such as by the US Food and Drug Administration (FDA) are being set in advance. But scientists and ethics experts are adamant that such processes must be transparent and adhere to sound principles of scientific integrity.
In July, the US top infectious diseases official Anthony Fauci said it was unlikely that the US would use vaccines developed by China or Russia, given their regulatory systems were far more opaque than those in the West.
Out of nine vaccines currently undergoing late-stage trials around the world, four are being developed in China. The fear is that China, with its more opaque system, could be cutting corners in the race to be first.
A surprise announcement last month by a representative from China National Biotec Group CNBG, also known as Sinopharm, a state-owned company and China’s largest vaccine manufacturer, revealed that hundreds of thousands of Chinese had already taken the two leading COVID-19 drugs being developed by the company even though late-stage human trials known as Phase 3 trials to confirm safety and efficacy were still not completed and fully assessed.
In July, China approved the emergency use of vaccines for specific groups deemed to be at high risk of exposure, including medical personnel and border officials. Beijing was the first city in China to start the emergency use programme. Tens of thousands of people – including workers at the Xinfadi food market, which was at the centre of the capital’s last major outbreak in June – have been given the Sinovac vaccine.
Another Chinese company Sinovac Biotech said in early September almost all its 3,000 employees and their families have been given its experimental coronavirus vaccine on a voluntary basis under China’s emergency use scheme that allows high-risk groups, including Chinese people working abroad, to receive vaccines not yet approved by regulators.
CNBG Chairman Yang Xiaoming said recently as many as 350,000 have already been administered one of the three experimental Chinese vaccines. Academics note these are all outside of the carefully monitored clinical trials under way in different countries and in advance of full regulatory approval in China. China claims that, so far, there have been no obvious reactions among those vaccinated.
Three of the four Chinese vaccine candidates in the final stage of clinical trials are inactivated vaccines – a simple technique that kills off the Sars-CoV-2 virus in a lab and uses it to trigger an immune response. A fourth COVID-19 vaccine being developed by China’s CanSino Biologics was approved for use by the Chinese military in June and is based on a weakened cold virus as a vector.
Trials in 10 countries
CNBG is conducting Phase 3 trials involving more than 40,000 volunteers in about 10 countries in Asia, Latin America and the Middle East. In exchange, China has promised millions of doses of vaccine will be shipped to those countries on a priority basis.
Sinovac, for example, promised to supply 40 million vaccines to Indonesia by March 2021.
João Doria, Governor of São Paulo, Brazil, said at a press conference on 1 October that the state had signed a US$90 million contract with Sinovac to receive 46 million doses of the Chinese company’s vaccine by the end of the year.
Sinovac’s Phase 3 clinical trials involving 13,000 volunteers around Brazil, all of them health professionals, would have to be completed and analysed by Brazil’s National Health Surveillance Agency, Anvisa, for approval before it can be distributed in Brazil, the Brazilian statement said.
CNBG is expected to complete phase 3 clinical trials in the United Arab Emirates in November. Earlier this month, Nawal al-Kaabi, the head of the UAE COVID-19 Clinical Management Committee, said that, of the 31,000 volunteers who took the Chinese vaccine, none experienced serious side effects. The UAE announced emergency approval of the vaccine for at-risk professions on 14 September making Sinopharm the first COVID-19 vaccine manufacturer to receive approval for use in a foreign country.
But little has been revealed about the research methodology and trial protocols of the Chinese companies.
Other countries involved in, or expecting to be involved in clinical trials of Chinese vaccines include Peru, Argentina, Bahrain, United Arab Emirates, Egypt, Pakistan, Turkey, Morocco, Saudi Arabia Bangladesh and Russia.
For some of these countries, hosting clinical trials is seen as a means of securing early access to vaccines, with many wealthy nations already securing supplies pending regulatory approval, and amid concerns that a World Health Organization mechanism to provide COVID-19 vaccines to poorer countries will cover only a small proportion of their populations.
Safety and ethical issues
China published data from Stage 1 and Stage 2 trials of its COVID-19 vaccine candidates in international journals. But the scale of experimental vaccine use has shocked many academics.
“Both from a legal as well as ethical standpoint there will be concerns about safety and efficacy,” said Calvin Ho, associate professor of law at the University of Hong Kong and an expert on legal, ethical and social implications of health and biotechnologies.
“We don’t really know how to monitor the situation so it’s quite different from the more conventional approach to vaccine development,” he told University World News, referring to national regulatory approval being granted only once there is sufficient safety and efficacy data.
“That’s different from a situation where it becomes a political exercise where these vaccines are provided to essentially politically friendly health systems, but don’t consider whether these health systems have the capacity to track the impact.”
Ho noted that China’s regulatory body is modelled on the US FDA and that regulators around the world share information but noted it was unclear how openly they share such information. “There is no foolproof approach,” he said.
“Given that there is huge competition [for a vaccine] going on, one might also wonder where that, when faced with such pressure regulators, might perhaps be less stringent in terms of their expectations,” Ho said.
“It means there need to be additional safeguards in place,” Ho said. These could include post roll-out surveillance and more considered thinking about who gets the vaccines. “You can’t just give them out to everybody and anybody.”
Angus Dawson, professor of bioethics at Australia’s University of Sydney School of Public Health told a recent online symposium organised by the Association of Pacific Rim Universities: “If you are talking about vaccination of six billion people [globally] even a very rare case [of side effects] will be something that might actually happen with many people.”
Hong Kong’s English language South China Morning Post newspaper said in an editorial this month that “with the disease having been unknown just 10 months ago, there are concerns that best practice is not being followed. Beijing already faces a trust deficit in the eyes of some in the world; it cannot afford to sacrifice safety and effectiveness in the rush to show its scientific and diplomatic prowess.
“But there can be no missteps. Beijing’s early efforts to help countries struggling with COVID-19 faltered when some companies’ testing kits and face masks were criticised for being substandard. Rules were quickly put in place to ensure quality. Earlier food and drug scandals have marred China’s reputation,” the newspaper said.
China joins COVAX
China appeared to be hoping to bolster global trust in its vaccines by this week joining COVAX, the global initiative for fair distribution of COVID-19 vaccines let by the WHO and the vaccine alliance Gavi.
China’s Foreign Ministry spokeswoman, Hua Chunying, said on Friday: “Even when China is leading the world with several vaccines in advanced stages of R&D and with ample production capacity, it still decided to join COVAX.
“We are taking this concrete step to ensure equitable distribution of vaccines, especially to developing countries, and hope more capable countries will also join and support COVAX.”
“Being within the COVAX setup might inspire greater confidence in the vaccine itself. Before WHO takes this on in terms of their emergency listing requirements they will still review the mechanisms in place and they will require data from the manufacturers. The Chinese manufacturers will also need to have secured regulatory approval from the Chinese authority,” Ho said.
Before emergency use approval
Sinopharm may have given experimental vaccines to 180 of its executives before they were even approved for human trials or given emergency use approval by the Chinese authorities.
Sinopharm chairman Liu Jingzhen, along with CNBG’s chairman Yang Xiaoming and vice-president Zhang Yuntao, had shots of their companies’ respective experimental vaccines in March, Zhang said recently.
Zhou Song, legal advisor at CNBG, said in a statement last month that in ongoing trials of the two candidate vaccines “there was not a single case that demonstrated significant negative effects, nor was anyone infected”.
“Tens of thousands of people vaccinated have travelled to countries and regions with high risks of COVID-19. No one has been infected so far, and this proved the effectiveness of the vaccines,” he said.
China has defended the use of experimental vaccines in this way saying the move was sanctioned by the World Health Organization (WHO).
At a media briefing on 24 September, Dr Mariangela Simao, the WHO’s assistant director-general for access to medicines and health products, said: “Countries have autonomy according to their national regulations and legislations to issue emergency use authorisations for any health product, and China and other countries have already done so for different products. And WHO has emergency use listing provisions and has issued already several products for diagnostics.”
Socorro Escalate, the WHO’s coordinator for essential medicines and health technologies in the Western Pacific region, told an online news conference that China had held preliminary discussions with the WHO to have its vaccines included in a list for emergency use which allows unlicensed vaccines and treatments to be assessed to make them available in public health emergencies. This helps WHO member states and UN procurement agencies to determine the acceptability of the vaccines.
“If Chinese producers are prepared to go through that particular phase with WHO then it would suggest that they are relatively confident about their product, otherwise it would be a matter of losing face [embarrassment] for producing a bad product and trying to put it out in the market,” HKU’s Ho said.
“WHO have a standardised approach to this kind of emergency approval but at the same time it’s under review – there is a consultation that is still ongoing.”
The norm is for pharmaceutical companies, even in the West, not to divulge patient information. But with intense public interest in a COVID vaccine, pharmaceutical companies like the UK’s AstraZeneca which has partnered with Oxford University are already talking about more transparency and ‘reasonable disclosures’, to shore up public trust.
And, despite pressure from US president Donald Trump for US pharmaceutical giants to have a vaccine by the US election on 3 November, US companies have resisted short-circuiting established safety protocols. Contrary to some expectations that it might lower the bar for emergency approval, the FDA told vaccine developers this week it would require at least two months’ worth of safety data to assess a vaccine for emergency use.
Ana Mari Cauce, president of Washington University, Seattle, which organised an online symposium on preserving the scientific integrity of COVID-19 vaccine development on 6 October jointly with Johns Hopkins University, said: “It is paramount for the safety of millions that the vaccine trial process be allowed to proceed with all the appropriate procedures, reviews and oversights even within the context of an accelerated process.
“Those checks aren’t just critical to the development of a safe and effective vaccine, they are also essential to maintaining and inspiring the public’s trust.”